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Behavioral Effects of Water Toxicity: An Unexpected Problem in Experimental Methodology
Behavioral Effects of Water Toxicity: An Unexpected Problem in Experimental Methodology
CSSS 004M
C.P. Ptition
Fluoration de
leau potable
Abstract
Are the effects of environmental toxins on brain chemistry and behavior
relevant to experimental methods in evolutionary psychology? The question is
raised by a study by Crabbe, Wahlsten and Dudek, who conducted six experiments
with eight mouse strains at three laboratories (Portland, Oregon; Albany, New York,
and Edmonton, Alberta). Results were influenced by unanticipated local factors.
Reanalysis of this study suggests that local drinking water, used in all sites, may
have contributed to a tendency for lower behavioral inhibition in Edmonton, where
public water supplies are treated with hydrofluosilicic acid. Although this chemical
and sodium silicofluoride are widely used in the U.S., neither of the silicofluorides is
added to the water in Portland or Albany. Silicofluorides are acetylcholinesterase
inhibitors whose use in water treatment has been associated with enhanced uptake
of environmental lead as well as increased disinhibition of behaviors likely to be
influenced by lead neurotoxicity. Granted prudence is needed when interpreting
correlational findings, two methodological conclusions follow: first, important
behavioral experiments may need replication using more than one genotype in
different sites; second, even an apparently innocuous variable such as tap water
may be a source of behavioral neurotoxicity (with unexpected effects on replicating
experimental outcomes).
* Foundation for Neuroscience & Society, Department of Government, Dartmouth
College, Hanover, NH. 03755 USA
**Intellequity Consulting, 430 Center Street, Newton, MA 02458
I.
In short, while expected behavioral differences were found between genetic mutant
strains, the three sites were significantly different on six of eight measures -- and on four
measures, there were statistically significant interactions between site and genotype in
observed behaviors.
To explain why the same procedures in Edmonton, Portland, and Albany yielded
different results, with the site influencing some genetic mutants in six cases but not
others, it is essential to identify the variables that were consciously controlled or known
to vary:
The experimenters did not suspect any of these "unmatched variables" but noted that
"specific experimenters performing the testing were unique to each laboratory and could
have influenced behavior of the mice. The experimenter in Edmonton, for example, was
highly allergic to mice and performed all tests while wearing a respirator -- a laboratoryspecific (and uncontrolled) variable." (Ibid., p. 1672).
Because functional mechanisms were not cited to explain the observed behavioral
variability attributed to these factors, further analysis is appropriate. ii
be useful to consider whether neurotoxic effects of chemicals in local tap water most
notably lead (or other heavy metals) and silicofluorides -- could have influenced the
behaviors that differed between laboratories in ways sometimes also dependent on mouse
strain. 1
Four steps are needed to formulate and test this hypothesis. First, precisely which
behaviors varied in each location? Second, among uncontrolled variables, why is tap
water a source of neurotoxicity that could produce these effects and if so, why is it
reasonable to test the toxicity hypothesis with data on the use of silicofluorides in water
treatment? Third, an empirical test of the hypothesis begins by determining whether
silicofluoride usage in public water at these three sites varied in a way consistent with the
experimental results. Finally, the empirical test concludes by comparing previously
reported data on behavioral effects of silicofluoride treated water with the experimental
results reported by Crabbe, Wahlsten, and Dudek. As will be shown, the toxins had
similar functional consequences in both animal and human studies with interactive effects
like those predicted by toxicogenomics.
After drafting this manuscript, publication of another anomaly in the Edmonton, Albert
water supply has appeared: Naomi Lubick, More nitrosamines in drinking water
Two nitrosamines, considered to be potential carcinogens, have been detected in drinking
water for the first time, Science News (Nov. 8, 2006),
http://pubs.acs.org/subscribe/journals/esthag-w/2006/nov/science/nl_nitrosamines.html.
For the original article: Yuan-Yuan Zhao, Jessica Boyd, Steve E. Hrudey, and Xing-Fang
Li, Characterization of New Nitrosamines in Drinking Water Using Liquid
Chromatography Tandem Mass Spectrometry, Environ. Sci. Technol.; 2006; ASAP Web
Release Date: 08-Nov-2006;DOI: 10.1021/es061332s
5
test the number of genetic strains that was most active, least active, intermediate, or the
same as at other sites. For the 32 tests at each site (8 genetic strains in each of four
experiments), mice in Edmonton were most active in 26 tests, while the number of
genetic strains in Portland or Albany that were of lowest activity differed by test and by
site.
The researchers present data for one more experiment -- the tendency of mice to
prefer ethanol to tap water as measured by the grams of ethanol consumed. For this
behavior, which concerns choice of liquid rather than locomotion, the researchers note
that "laboratory environment was not critical. For example, ethanol drinking scores were
closely comparable across all three labs, and genotypes alone accounted for 48 of the
variance." (Crabbe, Wahlsted, & Dudek, 1999; p. 1671). As Table 2 shows, while there
were differences between Portland and Albany among the 8 strains in this experiment,
responses were usually intermediate in Edmonton, suggesting that the results in Table 1
are not due to a consistent error in record-keeping. iii
These results are clearest when summarized as the proportion of the 32 locomotor
tests in each category at each site (Table 3). Whereas mice in Edmonton were the most
active in three-quarters of the 32 tests, those in Portland and Albany where either the least
active or intermediate in more than three-quarters of the tests. Hence the principal
research question concerns the factor or factors that increased locomotor behavior or
reduced behavioral inhibition in Edmonton.
6
1
0
1
1
4
2
1
0
1
7
0
Test #2: "Activity change after cocaine," Day 5 minus Day 1 (Fig 1B)
Most active
Intermediate
Least active
Same in all
4
1
1
2
1
2
3
2
1
4
1
2
7
1
0
0
1
2
5
0
0
4
4
0
7
0
0
1
0
1
7
0
0
5
2
1
SOURCE: Crabbe, Wahlsten, & Dudek, 1999. The ANOVA results include statistically
significant (p < .10) two-way interactions of genotype and site for at least one behavior in
each of these experiments (Table 1).
Most consumed
Edmonton
1/8
(12.5%)
Portland
4/8
(50%)
Albany
3/8
(37.5%)
Intermediate
4/8
(50%)
2/8
(25%)
1/8
(12.5%)
Least consumed
2/8
(25%)
1/8
(3.1%)
4/8
(50%)
1/8
(12.5%)
1/8
(12.5%)
0/8
(---%)
*Source: ibid., Fig. 3. ANOVA results show no statistical significance for site or for the
interaction of genotype and site (Ibid., Table 1).
Intermediate
Intermediate
Least active
Least active
Edmonton
24/32
(75%)
3/32
3/32
(9.4%)
1/32
1/32
(3.1%)
Portland
3/32
(9.4%)
9/32
9/32
(28.1%)
17/32
17/32
53.1%)
4/32
(12.5%)
3/32
(9.4%)
Albany
1/32
(3.1%)
14/32
14/32
(43.8%)
14/32
14/32
(43.8%)
3/32
(9.4%)
an
uncontrolled variable which has often been linked to uptake of heavy metals. This factor
is important because heavy metals are known to modify neurotransmitter function in
ways that could account for some of the behavioral differences noted in Tables 1-3
(Schauss, 1981; Marlow, Schneider, & Bliss, 1991; Brockel & Cory-Slechta, 1998).
For example, numerous studies show that lead is associated with lowered dopamine
function (especially in the basal ganglia) and, as a result, poor behavioral inhibition and
higher motor activity levels (Needleman, 1992; Cory-Sletcha, 1995).
Lead neurotoxicity has also been linked to increased response to given doses of
ethanol (Cezard, Demarquilly, Boniface, Haguencoer, 1992) and increased consumption
of cocaine, which compensates for reduced dopamine function (Kuhar, 1992; Slusher,
Tiffany, Olkowski, 1997).
Another toxin linked with several of these effects, including increased rates of
violent crime, is manganese, which downregulates serotonin as well as dopamine and
other neurotransmitters (Donaldson, Labella, & Gesser, 1981; Donaldson & Barbeau,
1985; Donaldson, 1987; Subhash & Pamashree, 1990; Gottschalk, Rebello, Buchsbaum,
Tucker, & Hodges, 1991). Since water systems sometimes contain potentially dangerous
levels of lead or manganese, tap water seems a plausible uncontrolled variable to explore
more fully as a source of between-laboratory differences in responses to the same
experimental paradigm.
This hypothesis is reinforced by considering the whether public water supplies are
treated with fluosilicic acid (H2SiF6) or sodium silicofluoride (Na2SiF6), a practice that
has been associated with both increased uptake of lead (and perhaps other toxins) from
the environment and greater behavioral disinhibition. Although these two chemicals
jointly called silicofluorides are widely used in water treatment in the U.S. and Canada,
they are toxins whose effects when injected in water were never tested for effects on
health and behavior (Thurnau, 2001). iv When fluoridaton using silicofluoride instead of
sodium fluoride was approved by the Public Health Service in 1950, this action was
based on a theoretical assumption that the compounds would dissociate virtually
completely (Zipkin & McClure, 1951). Earlier experiments in Europe were inconsistent
with this belief and more recent German studies revealed the persistence of residual
chemical species that have important biochemical effects (Rees & Hudleston, 1936; Ryss
& Slutskaya,, 1940; Westendorf, 1975). Moreover, three recent epidemiological studies
(population samples totalling over 400,000) indicate that, unlike sodium fluoride,
silicofluorides enhance lead uptake from environmental sources such as lead paint in old
housing or industrial pollution with lead (Masters & Coplan,1999; Coplan, Masters, &
10
Hone, 1999; Coplan, Masters, Hone, & Dykes, 2000; Masters, 2001). Combined with
human behavioral data on effects of silicofluoride-treated water (Masters, 2001; Masters,
Coplan, Hone, Grelotti, Gonzalez, & Jones, in press; Masters & Coplan, in press;
Masters, in press), there is reason to examine the hypothesis that use of municipal tap
water treated with these chemicals could modify mouse behavior.
To ascertain whether toxicity in local tap water helps explain enhanced locomotor
activity and reduced inhibition across divergent genetic strains in these experiments, there
are practical reasons to focus on silicofluorides. On the one hand, the only reliable
measure of lead or other toxic uptake in the experimental mice would have been analysis
of these chemicals in hair or blood at the time of the experiment. On the other,
silicofluoride usage in the experimental sites is documented and empirical studies have
associated silicofluoride treated water with acetylcholinesterase inhibition (Knappwost &
Westendorf, 1974; Westendorf, 1975) as well as enhanced lead uptake (e.g., Figures 1a-b
below) and behavioral differences like those in the Crabbe et al. experiments (e.g.,
Figures 2a-b below). v Hence silicofluorides provide a practical and theoretically
interesting way to check the toxicity hypothesis. vi
11
silicofluorides are today used in over 90% of fluoridated public water supplies, delivered
to approximately 140 million Americans, sodium fluoride (familiar from toothpaste) was
the chemical original tested for safety.
sodium fluoride and the silicofluorides (Coplan & Masters, 2001), testing the hypothesis
that silicofluoride-treated water was responsible for differing experimental results
between Edmonton and either Portland or Albany could benefit public policy as well as
research methods in evolutionary psychology.
12
The best data are FBI crime reports for all U.S. counties of
populations above 500,000, which show that controlling for lead pollution in the
environment, silicofluoride treated water is a risk factor for higher rates of violent crime
(for 1985: Figure 2a; for 1991: Figure 2b). That this is effect is not due to a spurious
correlation is shown by multiple regression analysis of this data: after controlling for
socio-economic, demographic, and other environmental variables associated with violent
crime, silicofluoride-treated water is a significant predictive factor for this type of
behavioral disinhibition (Table 4).
behavior also show that, controlling for other variables, silicofluoride usage is a
significant risk factor for loss of inhibition (Table 4). Because such arrests reflect
addiction and loss of inhibition rather than preference for ethanol (cf. Hyman & Malenka,
2001), these last results do not contradict the data on preference for ethanol in the
Edmonton samples studied by Crabbe et al. (see note 3 above).
The hypothesis that water treated with silicofluorides may have behavioral effects
is also confirmed by other data. In a National Institute of Justice study of cocaine use at
time of criminal arrest (n = 30,000), silicofluorides were significantly associated with
higher substance abuse (Masters & Coplan, 1999). And while reliable data on
hyperactivity (ADHD) among children are difficult to obtain, a private survey in
Massachusetts towns found that where silicofluorides are used, rates of learning
disabilities are higher, especially where lead levels in 90th % first draw water were above
20 ppb (Fig. 3).
Since these effects do not seem to occur where water is fluoridated with sodium
fluoride or not fluoridated at all, they support the hypothesis of water treatment chemistry
as a factor in higher locomotor activity and poor inhibition. Moreover, because the toxic
effects of silicofluorides differ by race, the human data is consistent with the differences
in mouse strain observed in the study by Crabbe, Wahlsten, and Dudek. While such
correlational data does not prove that silicofluoride treated tap water was a key factor,
13
it indicates the need for further laboratory experimentation on tap water as a potential
confounding factor in behavioral research.
Conclusion
By focusing simultaneously on genetic and environmental factors in behavior, the
study by Crabbe, Wahlsten, and Dudek was an important contribution. As two
commentators on this paper noted, in such studies evidence of interlab variability
generates controversies that stimulate further investigation, resulting in methodological
improvement over time. (Picciotto & Self, 1999). Consideration of an environmental
factor like local tap water is especially important because toxins often found in public
water supplies have known behavioral effects. Indeed, the irony in this case is that prior
studies in human toxicology may help explain experimental observations of mouse
behavior and contribute to improved laboratory techniques in evolutionary psychology.
14
In
15
FIGURE 1a
9
8
7
6
5
4
3
2
1
0
Race of Child
For NHANES III Children 3-5, mean blood lead is significantly associated with
fluoridation status (DF 3, F 17.14, p < .0001) and race (DF 2, F 19.35, p < .0001) as well
as for poverty income ratio (DF 1, F 66.55, p < .0001). Interaction effect between race
and fluoridation status: DF 6, F ;3.333, p < .0029. (Source: Masters, 2001).
16
FIGURE 1b
Significance, for ages 5-17: fluoridation status (DF 3, F 57.67, p < .0001), race (DF2,
28.68, p < .0001), Poverty-Income Ratio (DF 1, 252.88, p < .0001). Interaction between
race and fluoridation status DF 6, F 11.17, p < .0001 (Source:Masters, 2001).
17
FIGURE 2a.
(Source: Masters et al, in press; Masters & Coplan, in press). Lead Pollution is measured
by EPA Toxic Release Inventory
18
FIGURE 2b
19
Figure 3
Lead Levels in Public Water Supply: 90th % first draw sample of water had lead level above or
below 20 ppb. SiF: Community water supply does or does not use either fluosilicic acid or
sodium silicofluoride (SiFs) as fluoridation agents (CDC Fluoridation Census).
% Learning Disabilities: Results of authors informal survey. Sample is too small for statistical
reliability, but note same pattern found elsewhere: SiF enhances negative effects of lead pollution
in environment.
Lead in Water
< 20ppm
>20ppb
No SiF
n=7
n=1
SiF
n=2
n=5
Average % Learning Disabled Students by SiF use: No SiF = 10.2% (n=8)
SiF = 15.8% (n = 7):
20
References
Brockel B A, & Cory-Slechta D A. (1998) Lead, Attention, and Impulsive Behavior: Changes in
a Fixed-ratio Waiting-for-reward Paradigm, Pharmacology. Biochem. Behav. 60: 545-552;
Bryce-Smith, D, (1983) Lead Induced Disorder of Mentation in Children, Nutrition and Health
1: 179-194.
Castoldi, A.F.; Coccini T; Ceccatelli S; Manzo L. (2001) Neurotoxicity and molecular effects of
methylmercury, Brain Research Bulletin (May 15), 197-203.
Centers for Disease Control, Division of Oral Health (1993) Fluoridation Census 1992 (Atlanta,
GA : U. S. Department of Health and Human Services.
Cezard C, Demarquilly C, Boniface M, & Haguencoer J M. (1992) Influence of the Degree of
Exposure to Lead on Relations between Alcohol Consumption and the Biological Indices of Lead
Exposure, British Journal of Industrial Medicine 49: 645-647.
Coplan, M.J. & Masters, R.D. (1999). Is Silicofluoride Safe? Comments Re EPA Response to
Rep. Calvert's Inquiry Submission to Representative Kenneth Calvert, Subcommittee on
Energy and Science, Committee on Science, U. S. House of Representative (August 12, 1999).
Coplan, M.J., Masters, R.D., Hone, B., & Dykes, J E. (2000). Association of
Silicofluoride Treated Water with Elevated Blood Lead, Neurotoxicology 21: 10911100.
Coplan, M. J., Patch, S. C., Masters, R.D., Bachman, M. S., (2007), Confirmation of
and Explanations for Elevated Blood Lead and Other Disorders in Children Exposed to
Water Disinfection and Fluoridation Chemicals, Neurotoxicology, 38: 1032-1041.
21
Donaldson, J. & Barbeau, A. (1985 ). Metal Ions in Neurology and Psychiatry: Manganese
Neurotoxicity. In Neurology and Neurobiology, ed. Gabay, S; Harris, J; & Ho, B T (pp. 259-285)
New York: Alan R. Liss.
Donaldson, J, (1987) The Physiopathologic Significance of Manganese in Brain: Its Relation to
Schizophrenia and Neurodegenerative Disorders, Neurotoxicology: 8: 451-462;
Masters, R. & Coplan, M. (1999) Water Treatment with Silicofluorides and Lead
Toxicity, International Journal of Environmental Studies, 56: 435-49.
Masters, R. & Coplan, M. (1999). A Dynamic, Multifactorial Model of Alcohol, Drug Abuse,
and Crime: Linking Neuroscience and Behavior to Toxicology, Social Science Information,. 38:
591-624
Masters, R. D. (2001) Biology and Politics: Linking Nature and Nurture, Annual Review of
Political Science, 4: 345-69
Masters R D, Coplan, M. J., Hone, B.T., Grelotti, D. J., Gonzalez, D. & Jones, D. (1999). Brain
Biochemistry and the Violence Epidemic: Toward a Win-Win Strategy for Reducing Crime, in
Stuart Nagel, ed., Super-Optimizing Examples Across Public Policy Problems (NOVA Science
Publishers).
22
Environmental Pollution, Brain Chemistry, and Violent Crime," Gerald A. Corey Jr. &
Russell Gardner Jr., eds. The Evolutionary Neuroethology of Paul MacLean (Westport:
Praeger), pp. 275-296 (Ch. 15).
23
24
FIGURE 1a
9
8
7
6
5
4
3
2
1
0
Race of Child
For NHANES III Children 3-5, mean blood lead is significantly associated with
fluoridation status (DF 3, F 17.14, p < .0001) and race (DF 2, F 19.35, p < .0001) as well
as for poverty income ratio (DF 1, F 66.55, p < .0001). Interaction effect between race
and fluoridation status: DF 6, F ;3.333, p < .0029. (Source: Masters, 2001).
25
FIGURE 1b
Significance, for ages 5-17: fluoridation status (DF 3, F 57.67, p < .0001), race (DF2,
28.68, p < .0001), Poverty-Income Ratio (DF 1, 252.88, p < .0001). Interaction between
race and fluoridation status DF 6, F 11.17, p < .0001 (Source:Masters, 2001).
26
FIGURE 2a.
(Source: Masters et al, in press; Masters & Coplan, in press). Lead Pollution is measured
by EPA Toxic Release Inventory
27
FIGURE 2b
Figure 3
28
Lead Levels in Public Water Supply: 90th % first draw sample of water had lead level above or
below 20 ppb. SiF: Community water supply does or does not use either fluosilicic acid or
sodium silicofluoride (SiFs) as fluoridation agents (CDC Fluoridation Census).
% Learning Disabilities: Results of authors informal survey. Sample is too small for statistical
reliability, but note same pattern found elsewhere: SiF enhances negative effects of lead pollution
in environment.
Lead in Water
< 20ppm
>20ppb
No SiF
n=7
n=1
SiF
n=2
n=5
Average % Learning Disabled Students by SiF use: No SiF = 10.2% (n=8)
SiF = 15.8% (n = 7):
29
6
1
0
1
1
4
2
1
0
1
7
0
Test #2: "Activity change after cocaine," Day 5 minus Day 1 (Fig 1B)
Most active
Intermediate
Least active
Same in all
4
1
1
2
1
2
3
2
1
4
1
2
7
1
0
0
1
2
5
0
0
4
4
0
7
0
0
1
0
1
7
0
0
5
2
1
SOURCE: Crabbe, Wahlsten, & Dudek, 1999. The ANOVA results include statistically
significant (p < .10) two-way interactions of genotype and site for at least one behavior in
each of these experiments (Table 1).
30
Most consumed
Edmonton
1/8
(12.5%)
Portland
4/8
(50%)
Albany
3/8
(37.5%)
Intermediate
4/8
(50%)
2/8
(25%)
1/8
(12.5%)
Least consumed
2/8
(25%)
1/8
(3.1%)
4/8
(50%)
1/8
(12.5%)
1/8
(12.5%)
0/8
(---%)
*Source: ibid., Fig. 3. ANOVA results show no statistical significance for site or for the
interaction of genotype and site (Ibid., Table 1).
Intermediate
Intermediate
Least active
Least active
Edmonton
24/32
(75%)
3/32
3/32
(9.4%)
1/32
1/32
(3.1%)
4/32
(12.5%)
31
Portland
3/32
(9.4%)
9/32
9/32
(28.1%)
17/32
17/32
53.1%)
3/32
(9.4%)
Albany
1/32
(3.1%)
14/32
14/32
(43.8%)
14/32
14/32
(43.8%)
3/32
(9.4%)
Notes
i
See, respectively, the letters to Science by Larissa A. Phorecky; by Gerard B. Dawson, Jonathan
Flint, and Lawrence S.Wilkinson; by Ren Hen; and by Michael G. Tordoff, Alexander A.
Bachmanov, Mark I. Friedman, and Gary K. Beauchamp; and by Marina R. Picciotto and David
W. Self, in Testing the Genetics of Behavior, Science, 285 (1999) 2067. Another letter in this
group, by Marina R. Picciotto and David W. Self, refers to differences in investigators or
unforeseen environmental factors. That Crabbe, Wahlsten, and Dudek were aware of a wide
variety of potential confounding variations in experimental procedure is evident in the web site
giving details of procedures and test protocols (http://www.albany.edu/psy/obssr).
ii
In their reply to the letters cited in note 1, Crabbe, Wahlsten and Dudek do not exclude the
possibility that any of these factors might interact with genotype in producing different behaviors.
Indeed, they explicitly endorse the view of Picciotto and Self, who said: We should not conclude
from this study that behavioral analysis is beyond rigorous scientific investigation or that genetic
engineering will not help elucidate the molecular basis of complex behaviors. We should instead
use these results to highlight that scientific progress is a changing mosaic of overlapping studies
that correct, build, and expand on earlier findings. (ibid.) It might be added that, in assessing
the effect of the experimentor wearing a respirator in Edmonton, all sites had an exhaust fan
which could conceivably have masked this effect or substituted a comparable one.
iii
Although the authors do not explain this difference, they note that for the contrast between two
strains which had earlier differed four times on this test in Portland, there was no difference at
any site in the experiment reported in 1999 (Crabbe, Waldren, & Dudek, note 9). The authors
suggest that perhaps genes from the embryonic stem cell substrains might have subsequently
been fixed differentially in the 5-HT18+/+ and -/- strains maintained at Columbia University
(ibid.) Though an undetected variable (for example a change in animal care personnel) at
Portland is also mentioned (ibid), it is conceivable that prenatal or neonatal effects of some
environmental factor at the breeding laboratory influenced serotonergic functions linked to
alcohol consumption. Although mouse strains were originally reared in three different locations
(Bar Harbor, ME; Germantown, NY; and New York City ibid., note 3), the absence of reported
differences between mice shipped to experimental sites and their offspring reared on site would
seem to exclude this possibility. Such questions are relevant althoujgh the absence of a
preference for alcohol in Edmonton might seem to contradict the hypothesis presented below,
this is not the case. As for violent crime, an obvious example of disinhibition,analysis of U.S.
national data show that the percent of county population exposed to silicofluorides is strongly
predictive of arrest frequency for drunken behavior after controlling for manyh other variables
(Table 4). This finding does not contradict the experiment measuring preference for alcohol,
which is not predictive of addiction or its behavioral manifestations such as arrests for drunken
behavior (see Hyman and Malenka, 2001).
iv
they were unable to find any information on the effects of silicofluorides on health and
behavior.
v
Other considerations reinforce using silicofluoride to test the hypothesis that toxins in tap water
can modify behavior in a laboratory experiment. While exposure to heavy metals such as lead
could also explain the observed behavioral differences in the data of Crabbe et al., the actual
levels of lead, manganese, or other heavy metals in the tap water used in the experiment cannot
be reliably assessed ex post facto. While base-line levels of lead or manganese are often
recorded for an entire public water system, variations from one building to another can easily
confound these data. In addition, lead from paint in old housing or the pipes and pipe joints may
vary sharply from one building to another in the same community. Finally, if lead or other
toxins were present in other aspects of laboratory environments as well as in tap water,
silicofluoride-treated water could probably have been a factor increasing toxin uptake in the test
animals.
As will be shown below (Tables 1a-b), the importance of toxicogenomics in behavioral research
is underscored by its relevance to racial differences in human health and behavior. While not the
principal reason for encouraging this approach, it provides an substantial benefit (especially
insofar as some racial stereotypes may be influenced by the behavioral effects of neurotoxins).
For example, Table 4 shows that controlling for 15 other variables including percent of
population receiving water treated with silicofluorides, the percent of Blacks in a countys
population is no longer a significant predictor of violent crime and is negatively associated with
the rate of arrest for drunken behavior.
8
Myron J. Coplan, telephone call to Edmonton water quality laboratory (780-412-7638) on June
27, 1999. Jeffrey Kemnitz, telephone call to Epcor Water Services, Edmonton (703-412-7601) on
August 8, 2001.
viii
33
34
CSSS 004MA
C.P. Ptition
Fluoration de
leau potable
the silicon atoms dissociated from either H2SiF6 or Na2SiF6 cluster in what Finney et al describe
as "oligomerization of silicic acid to discrete oligosilicates and colloidal silica"
What this means in plain English is that unlike sodium fluoride (which leaves behind merely atoms of
sodium separated from atoms of fluorine), the silicon atoms from silicofluoride dissociation form
structures or sheets of silicate.
As the history of "silicon breast implants" might remind us, this formation of silicates can produce
dangerous biological changes, especially if the "oligosilicates and colloidal silica" are deposed in the
brain, since they can easily block neurotransmitter receptors that play important roles in regulating
behavior.
This is NOT merely a theoretical hypothesis: quite the contrary. Over a decade of peer-reviewed studies
has shown that where American public water supplies use either of the silicofluorides for water
fluoridation (which is the case for over 90% of artificially fluoridated water IN THE U.S.;sodium fluoride is
only used to fluoridate relatively small community water systems -- as is the case in Hanover, NH where
I live). Unlike sodium fluoride, public water treated with silicofluorides is significantly associated with
the following:
higher children's blood lead levels (due to greater absorption of lead from environmental exposures to
sources like old housing or industrial pollution)
lower grades in 9 different subjects and grades on the MCAS standardized educational tests use in
Massachusetts schools.
higher rates of arrest for driving under the influence of cocaine in New York state.
higher rates of violent crime in multivariate analyses (using up to 12 independent variables) of official
crime statistics for all
3141 counties in the U.S. (a study confirmed by separate analyses of violent crime data for 1985 and
1991).
Since none of these effects are observed where sodium fluoride is in use -- and the study by Finney et al.
confirms a significant difference in the side-effects of sodium fluoride and silicofluorides (in their study,
significant lowering of pH), it is not scientifically justifiable to consider water "fluoridation" without
reference to the compounds used for this purpose. Sodium fluoride is, to my knowledge, quite safe
when used as directed. In contrast, there is no research to my knowledge that contradicts the existence
of harmful side-effects where silicofluorides are added to water; rather, a recent manuscript has just
been sent me concerning unexpectly high levels of arsenic in much of the silicofluoride now use in the
U.S., which consequent harmful effects on consumers).
The side-effect of acetylcholinesterase inhibition (which had been found by Westendorf in Germany in
1974, and is confirmed by Finney et al) entails the inactivation of the enzyme breaking down the
neurotransmitter acetylcholine, which is a principal neurotransmitter activating motor behavior
throughout the human body. (Put simply, for body activity, acethylcholine is an "ON" switch, and
acetylcholinesterase is an "OFF" switch.
Putting silicofluorides in the water is therefore having the effect of turning the OFF switch OFF -- that is,
increasing bodily activity. In short,
while a complete experimental study has never been done, it would seem plausible to hypothesize that
among the factors responsible for the striking increase in rates of ADHD in the U.S., silicofluoride water
treatment deserves careful study. This is particularly important because the other effects of
silicofluoride treated water cited above (all of which have been documented in scientific publications)
can all be subsumed in the general functional category of poor behavioral inhibition or greater
impulsivity (which is reinforced by the higher blood lead levels).
I have enclosed three files as a summary of over a decade of research coauthored by Myron J. Coplan
(former Vice President of Albany Chemical, Inc.) and the undersigned.
Crabbe28b : is a reanalysis of animal studies in three cities, which revealed greater implusiveness in
the behavior of laboratory animals (as measured by the frequency of choosing dark arm of a "Y" maze in
a city using silicofluoride in water, whereas in the two other cities studied -- which didn't add
silicofluoride to tap water -- laboratory animals always preferred the lighted arm of the "Y" maze.)
Adverse Effects Silicic Acid2: is a summary of the side-effects of water treated with either fluorosilicic
acid or sodium silicofluoride.
SiFPubs7-28-11: is a bibliography of a decade of research on behavioral side effects of either H2Sif6 or
Na2SiF6, of which the other attachments are merely examples.
None of these studies (or others of which I'm aware) show comparable negative side-effects where
sodium fluoride is used in water fluoridation. As this indicates, the issue should NOT be "water
fluoridation"; rather, the scientific question concerns the safety of substituting silicofluorides (which on
one occasion were classified in Australia as "dangerous poisons" and are still considered "Hazardous"
compounds) for sodium fluoride.
If requested I will gladly present the foregoing information as a legal deposition sworn under oath. For
my credentials, feel free to consult WHO'S WHO IN AMERICA or other such documents.
Sincerely yours,
Roger D. Masters
Research Professor and Nelson A. Rockefeller Professor Emeritus, Department of Government,
Dartmouth College, Hanover, NH 0375t
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Mike:
I've had this enclosure, which you sent me on Mar. 18, in my files
since it
was first written -- and I frequently have had the following thought.
It seems it would be possible to shape this into an important
bibliographic
notice to submit for publication (whether to Joan Cranmer for publication
in
NEUROTOXICOLOGY and/or presentation to the next Neurotoxicology
conference, or
to another scientific publication). What do you think?
My point is that the manuscript should have the form of a bibliographic
essay on
a seriously neglected toxin (without primary reference to our work though
a
footnote listing our major publications would be appropriate).
I don't think much editorial tinkering is involved. I'd obviously prefer
that
you do this if you agree. However, if you would like me to play with it
for
your consideration, I'll give it a try.
For example, a possible introductory paragraph could read:
"This bibliographic note presents evidence that "silicic acid" is a
largely
ignored toxic compound which should be the subject of extensive research
due to
its potential for biochemical effects harmful to human health and
behavior.
Before presenting a bibliographic survey of what is known about this
compound, a
brief rationale is needed:
"ONE: What is Silicic Acid and Why Should It Be Studied Further? (bold
title)
(text on first page)
(bold title)
think appropriate.
"FOUR: Conclusion"
Any final remark (a single paragraph will do) on your view of what
needs
doing (starting of course with action on the NTP nomination).
AND in so
doing,
should that nomination be copied into the file?
You should of course be the sole author of this Research Note.
(I presume the half line "polymers registers with that of the repeat
units of
polypeptides" should be moved up to follow immediately the words "bonding
sites
of" (and before the structural sketch of oligomers of Si(OH)4.
--- Forwarded Message from MikeCoplan@aol.com -->From: MikeCoplan@aol.com
>Date: Wed, 18 Mar 2009 16:42:54 EDT
>Subject: Fwd: More re siliic acid
>To: Roger.d.Masters@Dartmouth.edu
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I. Publications
Masters, R,, Hone, B, and Doshi, A. (1998). Environmental Pollution, Neurotoxicity,
and Criminal Violence, in J. Rose, ed., Environmental Toxicology: Current
Developments (London: Gordon and Breach, 1998), pp. 13-48.
Survey of evidence linking lead and manganese neurotoxicity to aggressive
behavior and crime, presenting multivariate analysis correlating Toxic Release
Inventory for lead and manganese with crime data for 1991 from all 3141 US
counties Emphasizes effects of heavy metals on neurotransmitter function and
behavior.
Masters, Roger D., with Baldwin Way, Brian T. Hone, David J. Grelotti, David
Gonzalez, and David Jones (1998) "Neurotoxicity and Violence," Vermont Law Review,
22:358-382.
Legal implications of the evidence linking neurotoxicity and crime (including data
from Toxic Release Inventory and crime for partial sample of US counties)
Masters, R. and Coplan, M. (1999a) Water Treatment with Silicofluorides and Lead
Toxicity, International Journal of Environmental Studies, 56: 435-49
First published analysis of data linking silicofluoride treatment of public water
supplies with higher uptake of lead, focused on survey of childrens blood lead in
Massachusetts (by town).
Masters, R. and Coplan, M. (1999b) A Dynamic, Multifactorial Model of Alcohol, Drug
Abuse, and Crime: Linking Neuroscience and Behavior to Toxicology, Social Science
Information, 38:591-624.
Articulation of the linkages between neurotoxicity, brain chemistry,
environmental pollution, and behavior (with focus on substance abuse and crime),
using data from National Institute of Justice study of drug use in over 30,000
criminal offenders at time of arrest). Data show that where silicofluorides are in
use, criminals are more likely to consume alcohol, more likely to have used
cocaine at time of arrest and that communities have significantly higher crime
rates.
Page 1
Coplan, M.J. and Masters, R.D. (1999). "Is Silicofluoride Safe? Comments Re EPA
Response to Rep. Calvert's Inquiry" Submission to Representative Kenneth Calvert,
Subcommittee on Energy and Science, Committee on Scienc e, U. S. House of
Representative (August 12, 1999).
Analysis and rejoinder to letter dated 12 June 1999 from J. Charles Fox, Assistant
Administrator, EPA, to Hon.Kenneth Calvert, U. S. House of Representative,
commenting on errors and omissions in a "Question and Answer" statement and
"Fluorosilicate Fact Sheet" enclosed by Mr. Fox. This document contains a
preliminary review of scientific data on the differences between sodium fluoride
(NaF) and the silicofluorides (H2SiF6 and Na2SiF6), with an emphasis on the
complex production process and chemical interactions of the latter compounds.
Masters, R.D. and Coplan, M.J. (1999c). "The Triune Brain, the Environment, and
Human Behavior: Hommage to Paul MacLean," to appear in Russell Gardner, ed.
Festschrift in Honor of Paul MacLean . First presented at Back Bay Hilton Hotel,
Boston, Mass. July 16, 1999
Wilson, Jim (1999). The Chemistry of Violence, Popular Mechanics, (April), pp. 4243.
Journalist's report on Masters' earlier research on toxins and violence, and its
extension in collaborative work with Coplan.
Coplan, M.J. and Masters, R.D. (1999). "Is Silicofluoride Safe? Comments Re EPA
Response to Rep. Calvert's Inquiry" Submission to Representative Kenneth Calvert,
Subcommittee on Energy and Science, Committee on Science, U. S. House of
Representatives (August 12, 1999).
Analysis and rejoinder to letter dated 12 June 1999 from J. Charles Fox, Assistant
Administrator, EPA, to Hon.Kenneth Calvert, U. S. House of Representative,
commenting on errors and omissions in a "Question and Answer" statement and
"Fluorosilicate Fact Sheet" enclosed by Mr. Fox. This document contains a
Page 2
Myron J. Coplan and Roger Masters. 2001. Guest Editorial: Silicofluorides and
fluoridation, Fluoride Quarterly Journal of the International Society for Fluoride
Research, 34: 161-220.
Masters, R.D. (2002). MacLeans Evolutionary Neuroethology: Environmental
Pollution, Brain Chemistry, and Violent Crime," Gerald A. Corey Jr. & Russell Gardner
Jr., eds. The Evolutionary Neuroethology of Paul MacLean (Westport: Praeger), pp.
275-296 (Ch. 15).
Survey of research on neurotoxicity, brain chemistry and behavior, including
evidence of the role of lead and other heavy metal pollution and crime (as
demonstrated by individual data, neurochemistry, and both geographic and
longitudinal data) as well as survey of data linking silicofluorides to enhanced
lead uptake. First publication of findings on the extremely high correlation (r =
.90) between gallons of leaded gasoline sold and the crime rates sixteen years
later, confirming special vulnerability of pregnant mothers and newborns to lead
toxicity.
First presented at conference in 1999 (see under conference presentations).
Roger D. Masters, 2003. Neurotoxicology and Violence, in Richard W. Bloom and
Nancy K. Dess, eds., Evolutionary Psychology and Violence: A Primer for
Policymakers and Public Policy Advocates (Praeger/Greenwood), Ch. 2, pp. 23-56.
Page 3
Web-site:
Page 4
Page 5
Once again, average blood lead levels were significantly higher (p < .0001) in
communities using silicofluorides in water treatment than in those with
unfluoridated water. The effect was found independently in every age group for
three ethnic subsamples
Masters, R.D. and Coplan, M. J. (2001). Silicofluorides and Enhanced Lead Uptake,
Behavaioral Toxicology Society, ,annual meetings, Research Triangle Park, NC., May 6
Suvey of findings in research in this area.
Masters, R.D. (2002), Toxins and Behavior: Implications of Toxicogenomics for Public
Policy, Paper presented to XXth International Neurotoxicology Conference, Little Rock, ARKNov. 19.
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